Study of the tolerance and diuretic properties of torasemide following oral or intravenous administration to healthy volunteers

Abstract

The tolerance and diuretic properties of torasemide after oral or intravenous administration to healthy volunteers were studied. Six groups, each of 6 subjects, were given single rising oral doses ranging from 10 to 100 mg; 8 subjects received ascending i.v. doses on alternate days, ranging from 2.5 to 80 mg. At the highest oral doses investigated (80 mg and 100 mg) a number of volunteers complained of cramps in the knees, calves and feet. These symptoms were generally of short duration. Similar effects were not encountered during the intravenous study. There were no significant changes in ECG. Some significant drug-related changes were encountered in the within-study biochemistry and haematology assessments. Torasemide proved to be a potent diuretic following oral administration at all the doses investigated and following intravenous administration at all doses except 2.5 mg. A linear relationship existed between the urine output and the logarithm of the dose, and both sodium and chloride excretion were linearly correlated with urine volume. The rate of potassium excretion was markedly lower than that of sodium and chloride and was linearly correlated with the logarithm of the urine volume. Torasemide was well tolerated from all perspectives studied. It showed a potent diuretic property, and was equally effective by the oral and intravenous routes.

Torasemide, a New Loop Diuretic, in Patients with Chronic Renal Failure

“…These results may suggest that torasemide has a long-lasting diuretic activity. However, in normal volun teers and in patients with chronic renal failure torase mide exerted its maximal diuretic activity within the first 6 h [4,6,10,11,15]. Different experimental protocols can explain this discrepancy.…”

“…Its structural formula differs from the commonest loop di uretics [2][3][4]. Studies in dogs and rats have shown that torasemide is 5-10 times more potent [5] than furosemide and has a longer half live [2,6].…”

“…Clinical studies were carried out in healthy volunteers [4,7] and in patients with cardiac and/or hepatic diseases [6,8], In patients with chronic renal failure, torasemide was administered in single doses for pharmacokinetic evaluation [9][10][11], In this study, diuretic potency and duration of action were evaluated in patients with chronic renal failure treated with torasemide to correct both hypertension and fluid retention. Torasemide increased urine output and sodium excretion, correcting ECF volume expansion.…”

Long-term Efficacy of Torsemide Compared with Frusemide in Cirrhotic Patients with Ascites

“…We excluded patients with albumin serum-ascitic gradient less than 1.1 g/dl, renal failure (serum urea > 50 mg/dl and/or serum creatinine > 1. 5 Fifty-ve patients were excluded for the following reasons: gastrointestinal bleeding (20 patients), encephalopathy (10 patients), spontaneous bacterial peritonitis (10 patients), renal failure (5 patients), cardiac failure (2 patients), refusal to participate in the study (3 patients) and hepatocellular carcinoma (5 patients). The study was performed on the remaining 46 cirrhotic patients with ascites (27 males and 19 females; mean age, 55 § 11; range, 24-75) (Fig.…”

“…In short-term clinical trials, torsemide had greater and more prolonged natriuretic and diuretic effects in healthy subjects (5) and in cirrhotic patients with (6)(7)(8)(9) or without ascites (10) than frusemide in equipotent diuretic doses. The only longterm study comparing the effects of both loop diuretics associated to spironolactone concluded that both treatments had similar effects on urinary volume and fractional excretion of sodium, chloride, and uric acid.…”